Development and validation of a novel risk stratification algorithm for relapsed multiple myeloma.

Multiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease-related factors change between diagnosis and the initiation of second-line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K-adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)-4 (highest risk) were 61 center dot 6, 29 center dot 6, 14 center dot 2 and 5 center dot 9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations.